Pathophysiology of the behavioral variant of frontotemporal lobar degeneration: A study combining MRI and FDG-PET

Abstract

Gray matter (GM) lobar atrophy and glucose hypometabolism are well-described hallmarks of frontotemporal lobar degeneration (FTLD), but the relationships between them are still poorly understood. In this study, we aimed to show the patterns of GM atrophy and hypometabolism in a sample of 15 patients with the behavioral variant of FTLD (bv-FTD), compared to 15 healthy controls, then to provide a direct comparison between GM atrophy and hypometabolism, using a voxel-based method specially designed to statistically compare the two imaging modalities. The participants underwent structural magnetic resonance imaging and F-fluorodeoxyglucose (FDG) positron emission tomography examinations. First, between-group comparisons of GM volume and metabolism were performed. Then, in the patient group, correlations between regional alterations and direct between-modality voxelwise comparison were performed. Finally, we examined individual patterns of brain abnormalities for each imaging modality and each patient. The observed patterns of GM atrophy and hypometabolism were consistent with previous studies. We found significant voxelwise correlations between changes in GM and FDG uptake, mainly in the frontal cortex, corresponding to the typical profile of alterations in bv-FTD. The direct comparison revealed regional variability in the relationship between hypometabolism and atrophy. This analysis revealed greater atrophy than hypometabolism in the right putamen and amygdala, and left insula and superior temporal gyrus, whereas hypometabolism was more severe than GM atrophy in the left caudate nucleus and anterior cingulate cortex. Finally, GM atrophy affected the right amygdala/hippocampus and left insula in 95 % of the patients. These findings provide evidence for regional variations in the hierarchy of hypometabolism and GM atrophy and the relationships between them, and enhance our understanding of the pathophysiology of bv-FTD.

GRN mutation in a patient with a behavioral variant of frontotemporal lobar degeneration (bvFTD)

“…The 2010 brain MRI examination of our proband revealed not only asymmetric involvement with pronounced brain atrophy of the left temporal and frontal lobes and asymmetric caudate nucleus atrophy, which is in agreement with the literature [3,14], but also revealed greatly pronounced caudate nucleus and gyrus rectus atrophy on the left side, with virtually normal findings for the right caudate nucleus, and it would have been very interesting to follow the changes in asymmetry over time. Such a finding appears to be, according to some authors, a typical finding in bvFTD [8].…”

Comparison of Gray Matter Atrophy in Behavioral Variant Frontal Temporal Dementia and Amyotrophic Lateral Sclerosis: A Coordinate-Based Meta-Analysis

“…A flow diagram showing the identification and exclusion of studies is provided in Figure 1. Ultimately, a total of 37 studies were included in the meta-analysis, including 19 on bvFTD (one study included three bvFTD groups) (Rosen et al, 2002;Grossman et al, 2004;Boccardi et al, 2005;Kanda et al, 2008;Seeley et al, 2008;Ash et al, 2009;Kipps et al, 2009;Libon et al, 2009;Pardini et al, 2009;Hornberger et al, 2011;Farb et al, 2013;Massimo et al, 2013;Lagarde et al, 2015;Yokoyama et al, 2015;Dermody et al, 2016;Mandelli et al, 2016;Melloni et al, 2016;Buhour et al, 2017a;Bertoux et al, 2018) and 18 on ALS (Chang et al, 2005;Grosskreutz et al, 2006;Agosta et al, 2007;Mezzapesa et al, 2007;Thivard et al, 2007;Grossman et al, 2008;Cosottini et al, 2012;Tedeschi et al, 2012;Meoded et al, 2013;Cerami et al, 2014;Zhang et al, 2014;Devine et al, 2015;Raaphorst et al, 2015;Tavazzi et al, 2015;Zhu et al, 2015;Buhour et al, 2017b;Kim et al, 2017;Christidi et al, 2018…”

How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

“…59 In more details, hypometabolism was found in temporal regions in bvFTD. 41,60 In SD, hypometabolism was found in anterior poles, hippocampal region and fusiform gyrus. [61][62][63] Despite specific patterns of atrophy in each of the syndromes, ALS and FTD show many common areas of atrophy.…”